PXD026711-2

PXD026711 is an original dataset announced via ProteomeXchange.

Title	Low kindlin-3 levels in osteoclasts of kindlin-3 hypomorphic mice result in osteopetrosis due to leaky sealing zones
Description	Osteoclasts form special integrin-mediated adhesion structures called sealing zones that enable them to adhere to and resorb bone. Sealing zones consist mainly of densely packed podosomes tightly inter-connected by actin fibers. Their formation requires the presence of the hematopoietic integrin regulator kindlin-3. In the current study, we investigated osteoclasts and their adhesion structures in kindlin-3 hypomorphic mice expressing only 5-10% of kindlin-3. Low kindlin-3 expression reduces integrin activity, results in impaired osteoclast adhesion and signaling, and delays cell spreading. Despite these defects, in vitro generated kindlin-3-hypomorphic osteoclasts arrange their podosomes into adhesion patches and belts, which show abnormal podosome and actin organization. Remarkably, kindlin-3-hypomorphic osteoclasts form sealing zones when cultured on calcified matrix in vitro and on bone surface in vivo. However, functional assays as well as immunohistochemical staining and electron micrographs of bone sections showed that they fail to properly seal the resorption lacunae, which is required for secreted proteases to be able to digest bone matrix. This results in mild osteopetrosis. Our study reveals a new, hitherto understudied function of kindlin-3 as an essential organizer of integrin-mediated adhesion structures, such as sealing zones.
HostingRepository	PRIDE
AnnounceDate	2021-11-25
AnnouncementXML	Submission_2021-12-03_04:55:07.213.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Theresa Bock
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-15 05:45:11	ID requested
1	2021-11-25 08:12:27	announced
⏵ 2	2021-12-03 04:55:09	announced	2021-12-03: Updated publication reference for PubMed record(s): 34704600.

Klapproth S, Richter K, T, ü, rk C, Bock T, Bromberger T, Dominik J, Huck K, Pfaller K, Hess MW, Reichel CA, Kr, ü, ger M, Nakchbandi IA, Moser M, Low kindlin-3 levels in osteoclasts of kindlin-3 hypomorphic mice result in osteopetrosis due to leaky sealing zones. J Cell Sci, 134(22):(2021) [pubmed]

submitter keyword: Kindlin-3, osteoclast, integrin, podosome, sealing zone, bone resorption

Markus Moser
contact affiliation	Institute of Experimental Hematology, School of Medicine, Technische Universität München, Munich, D-81675, Germany; Max-Planck Institute of Biochemistry, D-82152 Martinsried
contact email	m.moser@tum.de
lab head
Theresa Bock
contact affiliation	CECAD Research Center, University of Cologne
contact email	tbock2@uni-koeln.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026711
     1. Label: PRIDE project
     2. Name: Low kindlin-3 levels in osteoclasts of kindlin-3 hypomorphic mice result in osteopetrosis due to leaky sealing zones